We will attempt to gain information about the motional behavior of proteins by studying the ability of these motions to allow a variety of small molecules to come into contact with normally buried protein groups. Target positions within the proteins will be fluorescent and phosphorescent tryptophans, porphyrins, and individual identifiable protons. Collisional encounters will be registered by the quenching of fluorescence and phosphorescence, by phosphorescence detected H-D exchange, and by 1H NMR T1 measurements. A wide range of proteins and small molecule agents will be studied. These methods are expected to distinguish between and partially characterize: 1) the small rapid liquid-like motions that may create transient channels accommodating the entry into the protein matrix of the small test molecules; 2) more sizeable opening reactions of the kind that may bring buried groups out into contact with the solvent. In addition other factors that may operate in governing protein-small molecule interactions will be studied, including the possibility of binding of the small molecules to and diffusion over the protein surface and the role of partial exposure rather than full burial.